Low-dose Gonal-f® in Ovulation Induction

Infertility Clinical Trial

— LoGo  

Official title:

A Multi-Centre, Two-Arm, Interventional, Phase IV Study to Evaluate Tailoring of Recombinant FSH Treatment in Subjects With Chronic Anovulation Using the Gonal-f® Prefilled Pen in Women Undergoing Ovulation Induction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01871532
• Other study ID #: EMR700623_535
• Secondary ID: 2012-003227-38
• Status: Completed
• Phase: Phase 4
• First received: June 4, 2013
• Last updated: February 18, 2015
• Start date: July 2013
• Est. completion date: March 2014

Study information

• Verified date: February 2015
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: National Institute for Health ResearchUnited Kingdom: Research Ethics CommitteeIreland: Irish Medicines BoardIreland: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This is a prospective, multicenter, open-label, comparative and parallel-group study of ovulation induction evaluating tailoring of Recombinant follicle stimulating hormone (FSH) treatment using the Gonal-f® prefilled pen in World Health Organization (WHO) Type 2 anovulatory subjects who have previously failed to conceive with clomifene treatment.

Description:

Subjects will enter a screening period of up to one month before being randomized at the Baseline Visit, which will occur on Day 1 of the subject's menstrual cycle. Each subject will then receive up to 4 weeks treatment with Gonal-f®. If adequate follicular development (assessed by transvaginal ultrasound) is achieved, the subject will proceed to administration of human chorionic gonadotropin (hCG) within 24-48hrs of last Gonal-f® injection (or according to standard site practice).

Following administration of hCG, subjects will attempt to become pregnant via intercourse or intrauterine insemination. The method of conception will be determined by the subject's requirements and standard practice at the clinic site.

All subjects will be followed up appropriately until confirmation of biochemical pregnancy (hCG + minimum 14 days) and clinical pregnancy (hCG + minimum 42 days, for subjects with positive biochemical pregnancy test).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 37 Years

Eligibility

Inclusion Criteria:

• Subjects eligible for ovulation induction treatment, where monofollicular development is the desired treatment outcome and the dose schedule outlined in the protocol is deemed appropriate

• Premenopausal female subjects, aged between 18 and 37 years inclusive

• Subjects desirous of pregnancy/willing to conceive

• Subjects who are infertile due to chronic anovulation demonstrated by cycle duration of greater than 35 days.

• Subjects who have been treated with clomifene citrate therapy, according to standard site practice, and have failed to ovulate and/or conceive

• Subjects with follicle stimulating hormone (FSH) and prolactin (PRL) serum values within the normal range in the early follicular phase

• Subjects with an overall total antral follicle count greater than 10 (of follicle size greater than or equal to 2 millimeter [mm] and less than 11 mm) (that is, total between both ovaries)

• Subjects with at least one patent tube, as documented by recent (within 2 years before treatment assignment) hysterosalpingography (HSG) or hysterosalpingo contrast sonography (HyCoSy)

• Subjects with normal uterine cavity, as documented by recent (within 2 years before treatment assignment) hysteroscopy, HSG or ultrasound scan

• Subjects with body mass index (BMI) greater than 20 and less than or equal to 32 kilogram per square meter (kg/m^2) (BMI is equal to body weight [kilogram {kg}] divided by Height * Height [square meter {m^2}])

• Subjects with negative cervical Papanicolaou (PAP) test conducted according to national guidelines and/or standard site practice

• Male partners of female subjects with sperm compatible with non-assisted fertilization or availability of donor sperm, as confirmed by the Investigator

• Subjects who are willing and able to comply with protocol requirements and have provided written, informed consent

Exclusion Criteria:

• Subjects with history of hypersensitivity to the investigational medicinal product (IMP) (active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f®) or any other drug used in the trial (that is, Ovitrelle)

• Subjects with ovarian enlargement or ovarian cyst unrelated to Polycystic Ovary Syndrome (PCOS), and of unknown origin on ultrasound

• Subjects with evidence of diminished ovarian reserve (cycle length less than 26 days; FSH above the upper limit of local serum FSH values, total antral follicle count [AFC] in both ovaries less than 10)

• Subjects with uterine pathology/abnormalities, which in the opinion of the Investigator could impair pregnancy evolution

• Subjects who have undergone three or more previous miscarriages

• Subjects with any previous extrauterine pregnancy

• Pregnant or lactating female subjects

• Subjects with abnormal gynecological bleeding of unknown etiology.

• Subjects with previous history of severe ovarian hyper stimulation syndrome (OHSS) (after clomifene treatment)

• Subjects who have evidence of current or previous pelvic inflammatory disease before treatment assignment

• Subjects with tumors of the hypothalamus and pituitary gland

• Subjects with ovarian, uterine or mammary carcinoma

• Subjects treated with clomifene citrate or gonadotropins within 1 month of the screening evaluation

• Subjects with any medical condition which, in the opinion of the Investigator, would prevent an effective response, such as primary ovarian failure, or malformations of the reproductive organs incompatible with pregnancy

• Subjects with any medical condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug

• Subjects with any clinically significant systemic disease (for example, insulin-dependent diabetes) or any contraindication to being pregnant and/or carrying a pregnancy to term

• An active substance abuser

• Known infection with human immunodeficiency virus (HIV), Hepatitis B or C virus in the trial subject or her male partner

• Subjects who are currently participating in another clinical trial

• Subjects who are unable to give written informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Monofollicular Development

Intervention

Drug:
• Gonal-f®

Locations

Country	Name	City	State
Ireland	Research Site	Cork
Ireland	Research Site	Galway
United Kingdom	Research Site	Cambridge
United Kingdom	Research site	Cheshunt
United Kingdom	Research Site	Derby
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Glasgow
United Kingdom	Research site	London

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of cycles with monofollicular development that is, only one follicle greater than or equal to 17 millimeter and no other follicles greater than or equal to 14 millimeter		up to 4 weeks	No
Secondary	Percentage of cycles with bifollicular development that is, only two follicles greater than or equal to 17 millimeter		up to 4 weeks	No
Secondary	Percentage of cycles with multifollicular development that is, three or more follicles greater than or equal to 14 millimeter		up to 4 weeks	No
Secondary	Percentage of ovulatory cycles		up to 42 days post human chorionic gonadotrophin (hCG) administration	No
Secondary	Percentage of cycles wherein hCG was not administered		up to 4 weeks	No
Secondary	Percentage of cycles resulting in clinical pregnancy		35-42 days post hCG administration	No
Secondary	Number of multiple pregnancy		35-42 days post hCG administration	No
Secondary	Number of fetuses		35-42 days post hCG administration	No
Secondary	Number of miscarriages after confirmation of clinical pregnancy		35-42 days post hCG administration	No
Secondary	Number of subjects with Ovarian Hyper Stimulation Syndrome (OHSS)		up to 42 days post hCG administration	Yes
Secondary	Duration of Recombinant Follicle Stimulating Hormone (rFSH) stimulation		up to 4 weeks	No
Secondary	Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) administered per cycle		up to 4 weeks	No
Secondary	Change from Baseline in Anti-Mullerian Hormone (AMH) levels at Week 4		Baseline and Week 4	No
Secondary	Testosterone levels		Baseline	No
Secondary	Sex Hormone Binding Globulin (SHBG) levels		Baseline	No